Duloxetine is an orally administered, balanced, dual serotonin and norepinephrine (noradrenaline) reuptake inhibitor that increases neural input to the urethral sphincter, thereby relieving the symptoms of stress urinary incontinence (SUI). Duloxetine 40 mg twice daily for 12 weeks reduced the median incontinence episode frequency (IEF) to a significantly greater extent than placebo in women with predominant symptoms of SUI. In most studies, Incontinence Quality of Life (I-QOL) questionnaire total scores were significantly improved compared with placebo. In a dose-escalation study in women with severe SUI scheduled for continence surgery, duloxetine 80-120 mg/day for 8 weeks significantly reduced IEF and increased I-QOL total scores compared with placebo, and caused 20% of recipients to reconsider their willingness to undergo surgery. Duloxetine or duloxetine plus pelvic floor muscle training (PFMT) were more effective in reducing the median IEF than PFMT alone or no treatment in women with SUI. Mean I-QOL total scores suggested that combination therapy was more effective than either therapy alone. Nausea was the most frequent adverse event and was the main cause for discontinuing duloxetine therapy.